To study the role of the sympathetic nervous system in control of the circulation in cardiovascular disease we will utilize a new sensitive radioisotope derivative assay for plasma catecholamines (CA) based on HPLC separation and measuring individually norepinephrine, epinephrine, and dopamine (DA). We will define adrenergic function in basal and stimulated states to establish the role that adrenergic mechanisms may play in patients with hypertension and their interaction with renin-angiotensin. Plasma DA measurements will provide a new approach to examining the biologic role of DA outside the central nervous system in hypertension and its response (if any) to volume alterations. Using plasma CAs we will also examine the role of adrenergic mechanisms in (1) heart failure in its response to vasodilator therapy, (2) angina, and (3) myocardial infarction and its complications. The clinical pharmacology of several specific cardiovascular drugs will also be studied in relation to their effects on both the circulation and adrenergic mechanisms. Propranolol will be evaluated for its potential effects on sympathetic outflow, including blood levels of the drug and its 4-hydroxy metabolite. Studies of minoxidil will be extended using a new method for its chemical measurement and we will re-examine its pharmacokinetics in hypertensive patients and its tissue distribution in experimental animals. Molecular structure studies of metabolites with potential biologic activity are proposed. Finally, quinidine will be reevaluated in relation to a new, highly specific method of its analysis in plasma, and studies of its effect on the circulation and its interaction with the adrenergic mechanisms will be correlated with plasma levels of the drug and its metabolites. Thus, we will investigate adrenergic function in cardiovascular disease and its interaction with pharmacologic agents using new chemical methodology to provide information relevant to greater understanding of these disease states and of their response to drug therapy.